Mosquito larvicide

ABSTRACT

Limonene (or alpha-pinene) is condensed with sesamol under aqueous acidic conditions to produce a mixture of two novel compounds which are useful as mosquito larvicides.

This is a division of our copending application Ser. No. 554,053, filedFeb. 27, 1975, now U.S. Pat. No. 3,954,991.

DESCRIPTION OF THE INVENTION

The invention relates to and has among its objects the provision of neworganic compounds and their use as mosquito larvicides. Further objectsof the invention will be evident from the following description whereinparts and percentages are by weight unless otherwise specified. Theabbreviation ppm used herein refers to parts per million.

One of the ways of controlling insect populations is to kill the insectlarvae. Generally, a larvicide is applied to the breeding places orhabitat of the insects where it destroys substantial numbers of thelarvae.

We have discovered that certain new organic compounds are effective asmosquito larvicides. When the compounds of the invention are applied tothe habitat of the mosquito, the larval population is substantiallyreduced.

The compounds of the invention contain the following nucleus: ##SPC1##

One aspect of the invention concerns the provision of a novelcomposition of matter being a mixture of two position isomers (ML-1 andML-2). These isomeric compounds are represented by the followingformulas: ##SPC2##

As can be seen from the formulas, ML-1 and ML-2 differ in the positionsof an isopropyl group and a methyl group. In ML-1, the methyl group isin position 2 and the isopropyl group is in position 11. In ML-2, themethyl group is in position 11 and the isopropyl group is in position 2.

Referring to Formulas II and III, each of the methyl and isopropylsubstituents may also be in either α or β configuration. Thecompositions of the invention may contain all of the stereoisomers ofML-1 and ML-2, or they may contain only one stereoisomer of each of thesaid position isomers.

The mixture of ML-1 and ML-2 is highly effective in killing mosquitolarvae. Generally, for such purpose the mixture is applied to thebreeding places of the mosquitos in a concentration about 1 to 10 ppm.Because the mixture of ML-1 and ML-2 is effective in very minorconcentrations, it is preferred that it be dissolved or suspended in anappropriate carrier prior to application to the breeding centers. Thesolution or suspension increases the bulk of the mixture and thus allowssmall amounts of ML-1 and ML-2 to be administered to the mosquito'shabitat. Solvents appropriate for this aspect of the invention should behighly volatile, such as acetone, ethyl ether, ethanol, benzene, xylene,and the like.

Usually, the composition of the invention contains ML-1 and M-2 inapproximately equal proportions. However, it is within the compass ofthe invention to use a mixture wherein either ML-1 or ML-2 predominates.In addition, it is also within the scope of the invention to use eitherML-or ML-2 individually as a mosquito larvicide.

Another aspect of the invention concerns the method of synthesizing ML-1and ML-2. This involves condensing limonene (or alphapinene) withsesamol under aqueous acidic conditions. The condensation is generallycarried out under reflux, which is maintained for approximately 24hours. Usually, an organic acid, preferably formic acid, is employed andthe concentration of acid in water is about 50%. Other acids which maybe used in accordance with the invention are acetic acid, propionicacid, citric acid, tartaric acid, and the like. The condensationproduces the desired mixture of ML-1 and ML-2, which are obtained freeof unreacted limonene and sesamol by conventional purification stepssuch as extraction and distillation under reduced pressure.

The synthesis of the invention is illustrated by the following formulas:##SPC3##

The mixture of ML-1 and ML-2 is useful in such form, as explained above,as a mosquito larvicide. It is within the compass of the invention,moreover, to fractionate the mixture into its ML-1 and ML-2 componentsor even to apply a higher degree of fractionation to isolate individualstereoisomers of either ML-1 or ML-2. For the fractionations one may usesuch known techniques as fractional distillation, preparative glc, orcolumn chromatography.

EXAMPLES

The invention is further demonstrated by the following illustrativeexamples.

EXAMPLE 1 Condensation of Limonene with Sesamol

A mixture of sesamol (13.8 g., 0.1 mole), limonene (13.6 g., 0.1 mole)and 500 ml. of 50% formic acid was refluxed for 24 hours and then cooledto room temperature. The mixture was extracted with ether and yielded anoil, which distilled at 140°-145°C. at 150 μ Hg. The distillate (23.8g., 87%) was a mixture of Ml-1 and ML-2, which were separated by columnchromatography on activity III alumina. The column was eluted with a95:5 mixture of Skelly F:ether. (Skelly F is a mixture of petroleumhydrocarbons boiling between 30° and 60°C.) ML-2 was eluted first as anoil and had the following nuclear magnetic resonance (nmr) spectrum at100 MHz in deuterated chloroform: a doublet (6 protons) at δ 0.95 (J =coupling constant = 7.0 Hz), a doublet (3 protons) at δ 1.09 (J = 7.0Hz), a multiplet (1 proton) at δ 2.57 (8 Hz half width), a singlet (2protons) at δ 5.80, a singlet (1 proton) at δ 6.35, and a singlet (1proton) at δ 6.42. High resolution mass spectrometry--found molecularweight of 274.1567--C₁₁ H₂₂ O₃ requires 274.1569.

ML-1 was eluted after ML-2 and exhibited the following nmr spectrum at100 Hz in deuterated chloroform: a doublet (3 protons) at δ 0.94 (J = 6Hz), a doublet (3 protons) at δ 1.03 (J = 6.0 Hz), a singlet (3 protons)at δ 1.29, a multiplet (1 proton) at δ 2.90 (8 Hz half width), a singlet(2 protons) at δ 5.78, a singlet (1 proton) at δ 6.34, and a singlet (1proton) at δ 6.39.

EXAMPLE 2 Mosquito Larvicide Test

A mixture of ML-1 and ML-2 (approximately 50:50) prepared as describedin Example 1 was dissolved in acetone. The solution was added to watersuch that the final concentration of the mixture (ML-1 and ML-2) on thewater was 10 ppm. Early fourth-instar larvae of Anophelesquadrimaculatus Say were exposed to the treated water and mortality wasdetermined after 24 hours of exposure.

The above experiment was repeated with the following change: TheML-1-ML-2 mixture was added to the water to produce a finalconcentration of 1 ppm. The results are summarized in the table below.

                  Table 1                                                         ______________________________________                                        Mosquito larvicide                                                                         Concentration Mortality after                                                 (ppm)         24 hrs. (%)                                        ______________________________________                                        50:50 ML-1:ML-2                                                                            10            92                                                 50:50 ML-1:ML-2                                                                             1            36                                                 ______________________________________                                    

Having thus described our invention, we claim:
 1. A compound of thestructure ##SPC4##
 2. A compound of the structure ##SPC5##
 3. A mixtureof the compounds of the structures ##SPC6##
 4. The mixture of claim 3wherein the designated compounds are in approximately equal proportionsby weight.